Neuroscience
Neuropathophysiology
The Neuropathophysiology Unit is interested in the genetic regulation of neural development and in the cellular and molecular basis of neurodevelopmental disorders, primarily congenital cerebellar ataxias. For many years, we have used the cerebellum as a model system, and have studied its development using neural cell lines, neural stem cells, primary neural progenitors, organotypic tissue sections, and genetically engineered mouse lines, several of which developed by us.
Research activity
Neurodevelopmental disorders
We are interested in the genetic regulation of neural development and in the cellular and molecular basis of neurodevelopmental disorders, primarily congenital cerebellar ataxias and autism spectrum disorders. We study cerebellar development using cell lines, neural stem cells, primary neural progenitors, organotypic tissue sections, and genetically engineered mouse lines, several of which developed in house. We have been characterizing a murine model of Joubert syndrome (JS), a multisystem disorder featuring cerebellar malformation and dysfunction, besides other neural and extraneural defects. While JS is regarded as a ciliopathy, recent evidence indicates that this disorder may be also due to a dysfunction of the DNA damage repair machinery. We are studying one of the genes mutated in this disease (Zfp423 / ZNF423) and its role, both in DNA repair and in various other aspects of cerebellar development, focusing on the defects observed in JS.
Axonal biology in ALS
Our group has also undertaken a study of axonal biology in murine models of a deadly degenerative disorder of upper and lower motor neurons known as amyotrophic lateral sclerosis (ALS). The repertoire of treatments available to delay disease progression in ALS is severely limited, mostly due to our sketchy understanding of the underlying cellular defects. ALS affects axons and presynaptic terminals belonging to long range fiber tracts, namely the corticobulbar/corticospinal tract and the motor component of peripheral nerves. ALS genes, such as TARDPB, may contribute to axonal RNA metabolism and their mutation may impair splicing and subcellular mRNA localization/maturation, affecting mRNA translation and promoting ribosome frameshifts or nonsense mediated mRNA decay. Since TDP43 directly or indirectly appears to regulate translation, assessing any dysregulation in this process is a highly relevant, yet understudied, topic in ALS research.
